Details
Stereochemistry | RACEMIC |
Molecular Formula | C18H23NO.ClH |
Molecular Weight | 305.842 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
Cl.CN(C)CCOC(C1=CC=CC=C1)C2=CC=CC=C2C
InChI
InChIKey=UQZKYYIKWZOKKD-UHFFFAOYSA-N
InChI=1S/C18H23NO.ClH/c1-15-9-7-8-12-17(15)18(20-14-13-19(2)3)16-10-5-4-6-11-16;/h4-12,18H,13-14H2,1-3H3;1H
Molecular Formula | ClH |
Molecular Weight | 36.461 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Molecular Formula | C18H23NO |
Molecular Weight | 269.3813 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
DescriptionSources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Prntlbl.pdfCurator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB01173 | https://www.drugs.com/cdi/orphenadrine.html
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/anda/99/40249_Orphenadrine%20Citrate_Prntlbl.pdf
Curator's Comment: description was created based on several sources, including
https://www.drugbank.ca/drugs/DB01173 | https://www.drugs.com/cdi/orphenadrine.html
Orphenadrine is an anticholinergic drug of the ethanolamine antihistamine class used to treat muscle pain and to help with motor control in Parkinson's disease but has largely been superseded by newer drugs. Orphenadrine binds and inhibits both histamine H1 receptors and NMDA receptors. It restores the motor disturbances induced by neuroleptics, in particular, the hyperkinesia. The dopamine deficiency in the striatum increases the stimulating effects of the cholinergic system. This stimulation is counteracted by the anticholinergic effect of orphenadrine. It may have a relaxing effect on skeletal muscle spasms and it has a mood elevating effect. Orphenadrine is indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Orphenadrine is an anticholinergic with a predominantly central effect and only a weak peripheral effect. In addition, it has mild antihistaminic and local anesthetic properties. Parkinson's syndrome is the consequence of a disturbed balance between cholinergic and dopaminergic neurotransmission in the basal ganglia caused by a decrease in dopamine. Orphenadrine restores the physiological equilibrium and has a favorable effect on the rigidity and tremor of Parkinson's disease and Parkinsonian syndromes. Adverse reactions of orphenadrine citrate are mainly due to the mild anticholinergic action of orphenadrine citrate and are usually associated with higher dosage. Dryness of the mouth is usually the first adverse effect to appear. When the daily dose is increased, possible adverse effects include tachycardia, palpitation, urinary hesitancy or retention, blurred vision, dilatation of pupils, increased ocular tension, weakness, nausea, vomiting, headache, dizziness, constipation, drowsiness, hypersensitivity reactions, pruritus, hallucinations, agitation, tremor, gastric irritation and rarely urticaria and other dermatoses
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL231 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22793499 |
97.7 µM [IC50] | ||
Target ID: CHEMBL2094124 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9464369 |
6.0 µM [Ki] | ||
Target ID: CHEMBL2094109 Sources: https://www.ncbi.nlm.nih.gov/pubmed/3353357 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | DISIPAL Approved UseOrphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Launch Date1957 |
|||
Primary | DISIPAL Approved UseOrphenadrine citrate extended-release tablets are indicated as an adjunct to rest, physical therapy, and other measures for the relief of discomfort associated with acute painful musculoskeletal conditions. Launch Date1957 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
41.89 ng/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
49.19 ng/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
1739.15 ng × h/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
1772.44 ng × h/mL |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
21.02 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED |
|
22.29 h |
100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered: |
ORPHENADRINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7% |
ORPHENADRINE plasma | Homo sapiens |
Doses
Dose | Population | Adverse events |
---|---|---|
500 mg 1 times / day steady, oral Highest studied dose Dose: 500 mg, 1 times / day Route: oral Route: steady Dose: 500 mg, 1 times / day Sources: |
unhealthy, adult |
|
2 g single, intramuscular Overdose Dose: 2 g Route: intramuscular Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: |
2 g single, intravenous Overdose Dose: 2 g Route: intravenous Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: |
2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Other AEs: Toxic reaction (NOS)... Other AEs: Toxic reaction (NOS) (grade 5) Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Toxic reaction (NOS) | grade 5 | 2 g single, intramuscular Overdose Dose: 2 g Route: intramuscular Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Toxic reaction (NOS) | grade 5 | 2 g single, intravenous Overdose Dose: 2 g Route: intravenous Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Toxic reaction (NOS) | grade 5 | 2 g single, oral Overdose Dose: 2 g Route: oral Route: single Dose: 2 g Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
partial | ||||
partial | ||||
partial | ||||
partial | ||||
strong | ||||
strong | ||||
strong | ||||
weak [IC50 65 uM] | ||||
weak [IC50 >100 uM] | ||||
weak [IC50 >100 uM] | ||||
yes [IC50 2.5 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/12813002/ |
yes |
PubMed
Title | Date | PubMed |
---|---|---|
Prochlorperazine in childhood: side-effects. | 1977 |
|
Involvement of CYP2B6 in n-demethylation of ketamine in human liver microsomes. | 2001 Jun |
|
Acute intoxication with orphenadrine and clozapine. | 2001 Nov 15 |
|
Nefopam, an analogue of orphenadrine, protects against both NMDA receptor-dependent and independent veratridine-induced neurotoxicity. | 2002 |
|
Zebrafish embryos express an orthologue of HERG and are sensitive toward a range of QT-prolonging drugs inducing severe arrhythmia. | 2003 Dec 15 |
|
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes. | 2003 Jan 1 |
|
Upregulation of cytochromes P450 2B in rat liver by orphenadrine. | 2003 Jun |
|
Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia. | 2003 Nov 17 |
|
Analgesic effects of low-dose intravenous orphenadrine in the state of capsaicin hyperalgesia. A randomised, placebo-controlled, double-blind cross-over study using laser somatosensory evoked potentials obtained from capsaicin-irritated skin in healthy volunteers. | 2004 |
|
Phase II study of weekly paclitaxel and trastuzumab in anthracycline- and taxane-pretreated patients with HER2-overexpressing metastatic breast cancer. | 2004 Jan 12 |
|
Multicentric phase II trial of gemcitabine plus epirubicin plus paclitaxel as first-line chemotherapy in metastatic breast cancer. | 2004 Jan 12 |
|
Objective high-frequency tinnitus of middle-ear myoclonus. | 2004 Mar |
|
NMDA receptor in nucleus accumbens is implicated in morphine withdrawal in rats. | 2004 Nov |
|
Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease. | 2004 Oct |
|
Alternatives to levodopa in the initial treatment of early Parkinson's disease. | 2005 |
|
[Comparative study between botulin toxin and bupivacaine for triggering-points infiltration in chronic myofascial syndrome.]. | 2005 Apr |
|
Metabolism of territrem B and C in liver microsomes from 14-wk-old Wistar rats is catalyzed by cytochrome P-450 3A. | 2005 Feb 27 |
|
Dimemorfan N-demethylation by mouse liver microsomal cytochrome P450 enzymes. | 2005 Jul 1 |
|
Long QT syndrome in a patient with allergic rhinoconjunctivitis and auto-immune diabetes: focus on the choice of anti-H1 drugs. | 2006 Dec |
|
Torsades de pointes in congenital long QT syndrome following low-dose orphenadrine. | 2006 May |
|
A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer. | 2006 May 24 |
|
OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. | 2006 Nov |
|
Effects of enzyme inducers and inhibitors on the pharmacokinetics of metformin in rats: involvement of CYP2C11, 2D1 and 3A1/2 for the metabolism of metformin. | 2006 Oct |
|
Efficacy and safety of combined piroxicam, dexamethasone, orphenadrine, and cyanocobalamin treatment in mandibular molar surgery. | 2006 Sep |
|
Acute adverse cutaneous reaction after the concomitant use of venlafaxine and orphenadrine citrate plus paracetamol in a depressed patient. | 2006 Sep |
|
Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction. | 2006 Sep |
|
Characterization of antihistamine-human serum protein interactions by capillary electrophoresis. | 2007 Apr 20 |
|
Evaluation of enantioselective binding of basic drugs to plasma by ACE. | 2007 Aug |
|
Effect of warnings in a medical journal on the use of orphenadrine. | 2008 Aug |
|
Pharmacokinetic, metabolism and withdrawal time of orphenadrine in camels (Camelus dromedarius) after intravenous administration. | 2008 Dec |
|
Genetic and chemical modifiers of a CUG toxicity model in Drosophila. | 2008 Feb 13 |
|
Effects of CYP inducers and inhibitors on the pharmacokinetics of intravenous theophylline in rats: involvement of CYP1A1/2 in the formation of 1,3-DMU. | 2008 Jan |
|
Characterization of aconitine-induced block of delayed rectifier K+ current in differentiated NG108-15 neuronal cells. | 2008 May |
|
Demographics of toxic exposures presenting to three public hospital emergency departments in Singapore 2001-2003. | 2009 Apr |
|
Concordant up-regulation of cytochrome P450 Cyp3a11, testosterone oxidation and androgen receptor expression in mouse brain after xenobiotic treatment. | 2009 Apr |
|
Evaluation of luciferin-isopropyl acetal as a CYP3A4 substrate for human hepatocytes: effects of organic solvents, cytochrome P450 (P450) inhibitors, and P450 inducers. | 2009 Aug |
|
The use and potential abuse of anticholinergic antiparkinson drugs in Norway: a pharmacoepidemiological study. | 2009 Feb |
|
The first asymmetric halogen/metal-exchange reaction: desymmetrization of alcohols with enantiotopic bromoarene substituents. | 2009 Jul 6 |
|
Trends in the molecular pathogenesis and clinical therapeutics of common neurodegenerative disorders. | 2009 Jun 3 |
|
Determination of orphenadrine plasma levels using HPLC with diode array detection and a novel solid-phase extraction procedure in psychiatric patients. | 2009 Oct 15 |
|
Orphenadrinium picrate picric acid. | 2010 Feb 24 |
|
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2. | 2011 Jul 14 |
Patents
Sample Use Guides
Acute musculoskeletal conditions: 100 mg orally twice a day (morning and evening) or 60 mg by intramuscular or intravenous injection. May repeat every 12 hours.
Quinine-resistant leg cramps: 100 mg orally at bedtime.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/3353357
An aliquot (400 mkl) of the brain membrane suspension (0.14 mg of protein), 100 mkl of (-)3H-QNB (0.95 nM) (specific activity 46 Ci/mmol), and 50 mk1 of the competing drugs at various concentrations were preincubated for 10 min. and thereafter incubated for 60 min. at 25C in 50 mM Tris-HC1 buffer (PH 7.4). When binding to heart and lung membranes was studied, 500 nkl of homogenate (protein contents were 0.58 mg and 0.54 mg of rat heart and lung tissue and 0.63 mg of guinea pig lung tissue was added to tubes containing 500 mkl of 50 mM Tris-HC1 buffer (PH 7.4), 100 mk1 of (-)3H-QNB (final concentration 0.4 nM) and 100 mkl of buffer (total binding) or unlabeled Orphenadrine.
Substance Class |
Chemical
Created
by
admin
on
Edited
Mon Mar 31 18:27:53 GMT 2025
by
admin
on
Mon Mar 31 18:27:53 GMT 2025
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Record UNII |
UBY910DUXH
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Record Status |
Validated (UNII)
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Record Version |
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WHO-VATC |
QN04AB02
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WHO-ATC |
N04AB02
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NCI_THESAURUS |
C29704
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C78075
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202723
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DTXSID5025815
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82357
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UBY910DUXH
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DBSALT001021
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9568
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60902
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341-69-5
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100000085503
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SUB03547MIG
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206-435-4
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CHEMBL900
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Orphenadrine hydrochloride
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PARENT -> SALT/SOLVATE |
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ACTIVE MOIETY |